The Prevalence and Trends of Hepatitis B, Hepatitis C, and HIV among Voluntary Blood Donors in Kohgiluyeh and Boyer-Ahmad Transfusion Center, Southwestern Iran.

Background
Transfusion transmissible infections (TTIs) are a common complication of blood transfusion. Evaluation and monitoring the prevalence rate of TTIs in blood donors is a valuable indicator of donor selection and blood safety. We analyzed the trends of these infections among blood donors at Kohgiluyeh and Boyer-Ahmad transfusion service (KBTC) during 10 years.


Methods
Viral screening and confirmatory tests were carried out on 180304 voluntary donations from 2005-2014. The annual prevalence rates of hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV infections per 100000 donations and 95% confidence interval were calculated. Chi-square test was applied to obtain the P-value.


Results
The overall prevalence was 0.13% for HBV and 0.06% for HCV while there were only three positive cases for HIV. The annual trend fluctuated during the time period studied. Compared to first-time donors, regular and repeat donors were significantly less likely to be positive for these infections. Outstandingly, this study provides first data in TTIs seropositivity rates among blood donors in our region; surprisingly were lower compared to other reports of Iran.


Conclusion
The trends of TTIs prevalence in this study provide additional evidence that safety measures employed by the KBTC have been effective in maintaining a safe blood supply. The lower prevalence of TTIs in our study compared with other Iranian studies and also the general population reflects the efficacy of donor selection and education procedures in KBTC.


Introduction
Each year, more than 90 million blood units are collected in blood transfusion centers around the world (1); one-third of the world population will require blood transfusions or blood products at some point during their lifetimes. Blood transfusions do save millions of lives but unhealthy blood transfusions can have catastrophic health consequences on recipients, their families and on society in terms of economic costs (1,2). Thus, providing safe blood and blood products is a universal concern (3). Any recipient is at risk of transfusion-transmissible infections (TTIs), including the human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) (1). Among these, HBV and HCV infections represent a special concern (4) due to the higher risk of transmission via blood and blood products (5). HBV is one of the most common sources of chronic liver morbidity (6) while HCV is the major cause of post-transfusion hepatitis which, can result in chronic infections, cirrhosis and hepatocellular carcinoma (7). The worldwide prevalence of HBV and HCV in carrier status is estimated at about 350 million and 150 million infections, respectively (4). "In Iran, screening of blood donations for the HBV surface antigen (HBsAg), HIV and HCV became mandatory in 1974, 1989 and 1996, respectively" (8). Although, the rate of TTI transmission in recipients has been reduced drastically by employing the pre-donation questionnaires, donor education, voluntary donation, donor deferral and the use of advanced donor screening assays (4,(9)(10)(11), it has not been completely eliminated due to factors such as genetic variations in infectious agents, silent carriers, laboratory errors and variations in window periods (4,12,13). Therefore, these infections remain an important public health problem; special attention is being given to ensuring that blood transfusion organizations, particularly in developing countries, are making plans to decrease the prevalence trends of these infections (2). Evaluating TTI trend is a critical approach to monitoring the effectiveness of donor education, selection, and screening methods, leading both to supplying safe blood resources and obtaining a good estimate on the epidemiology of these infections in the population (3,7,14). The aim of this 10-year retrospective study was to assess the changes in prevalence trends of TTI infections among first-time, regular and repeat blood donors who attended the Kohgiluyeh and Boyer-Ahmad transfusion service, Kohgiluyeh and Boyer-Ahmad Province, Iran, from 2005-2014. To the best of our knowledge, no previous study of TTI prevalence trends over time had been carried out in the current study population.

Materials and Methods
This retrospective study was conducted at the Kohgiluyeh and Boyer-Ahmad Blood Transfusion Center (KBTC). All voluntary, nonremunerated blood donors who donated blood from 2005-2014 were investigated. The donors were selected based on the standard pre-donation screening process, including a health history questionnaire and physical examination. Donors were divided into three groups: first-time donors who were donating for the first and only time; regular donors who donated more than once during a year; and repeat donors who had a history of the previous donation, but the interval between two donations was longer than a year. All 180304 donated units were screened for HBsAg, HCV Ab and HIV (Ag/Ab) by ELISA based on IBTO instructions. HBsAg was detected using Behring, Simens, and Biorad kits, anti-HCV was detected by Orto, Biomerieux, Hepanostika, Biomedical, and Murex kits and HIV-Ab was detected by Vironostika, Biomerieux, Biorad, and Adaltis kits. The initially reactive samples were evaluated again; the repeatedly reactive ones were considered seropositive. Hepatitis B core antibody (anti-HBc) and HBsAg neutralization tests (Behring, Marburg, Germany), HCV recombinant immunoblot assay (RIBA) (Inonogenetic, Ghent, Belgium) and HIV western blots (Inonogenetic, Ghent, Belgium) were undertaken for all repeatedly positive samples. HIV p24 antigen was done for the HIV western blot -negative samples and monoclonal neutralization assay was carried out if the results were repeatedly reactive. Statistical analysis was performed using SPSS software (ver. 16.0, Chicago, IL, USA). To evaluate the infection trends, the prevalence of TTIs per 100000 donations was reported separately among first-time, regular and repeat blood donors.

Results
Over a period of 10 yr ( 2014  23743 4238  5489  14016  8  8  0  0  34  189  0  0  2013  23880 5121  4888  13871  5  4  0  1  21  78  0  7  2012  25540 7069  4649  13822  11  7  3  1  43  99  65  7  2011  22587 7482  3601  11504  10  9  1  0  44  120  28  0  2010  17094 6108  3223  7763  5  3  2  0  29  49  62  0  2009  13845 3320  2881  7644  18  17  1  0  130  512  35  0  2008  13670 3127  2534  8009  24  22  1  1  176  704  39  12  2007  13712 3505  2140  8067  12  11  0  1  88  314  0  12  2006  13270 4143  1544  7583  11  9  1  1  83  217  65  13  2005  12963 5720  762  6481  11 (25) and Ethiopia (25%) (26). However, our reported figure was higher than Australia, which had a rate of only 0.01% (27). As in our findings, HBV was the most common infection identified among first-time donors in the United Kingdom and Australia (7,28). Overall, the findings of this study provide additional evidence that the procedures employed by the KBTC are very effective in maintaining a safe blood supply. Given the increasing trends of HBV and HCV among first-time donors in 2014, data on demographic and risk factors should be collected from positive cases (7). With less than 1% HCV prevalence in the general population, Iran is considered a country with low incidence of the infection (29). HCV prevalence varies noticeably in different regions of Iran (30). In our study, the overall frequency of HCV during the ten years from 2005 to 2014 was determined to be 0.06%. That was lower than in other studies conducted on Iranian blood donors (3,7,8). The pooled prevalence rate of HCV among Iranian blood donors in different provinces and cities was 0.5%. However, variable results were obtained (32). The finding of the present study is inconsistent with other countries, such as Ethiopia with 13.3% (27), Pakistan with 4.06% (23), Cameron with 4.8% (33), Nigeria with 0.86% (24) and India with 0.84% (19). Furthermore, our finding was lower than the prevalence of HCV infection in the general population in Iran, as expected (21). Similar to HBV, an increasing trend of HCV prevalence was observed among first-time blood donors during 2005-2008, and then it declined significantly during 2008-2010. During the subsequent time period studied, it fluctuated, peaking in 2014. This increasing pattern in 2014, also seen for HBV, might be due to several issues, including the use of different screening reagents, changes in population risk factors and improvements in the donor screening procedure. In addition, physicians' incentives were reduced due to various reasons, such as insufficient salary so, as they did not take enough time for the patients' examinations, which could result in the TTI increment. Now, IBTO has chosen some strategies to increase their incentives. Increased cultural diversity and the expansion of relations with other societies, especially Persian Gulf countries, may be other reasons for the TTI increase in our population. These factors may have led to an increase in the number of confirmed positives. Furthermore, the low number of blood donations may also have biased the results. In this study, the trend in prevalence's of TTIs was in accordance with the confidential unit exclusion rate. In other words, with reduction in CFU, the prevalence's were reduced while the increase in CFU resulted in higher prevalences. A gradual decline in HCV prevalence in blood donations from, 0.14% in 2005 to 0.12% in 2007 was found (8). In comparison with the results obtained in other countries, the declining trend in HCV prevalence was ascribed among Canadian donors during 1993-2006 to a distinct reduction of HCV infection among first-time donors (34). A similar declining trend was reported among blood donors in the United States from 1999-2008 (35). Moreover, our study showed that HBs-Ag and HCV positivity rates among regular and repeat donors were significantly lower than for first-time donors. This is consistent with other studies (8,36). However, the observed difference in prevalence rates is not unexpected, due to the removal of positive cases among regular and repeat donors by donor selection criteria or testing. Similar findings that first-time donors show higher rates of infections were also reported in other studies in Australia (33), the United Kingdom (37) and the Netherlands (38). Voluntary, regular and repeat blood donors constitute the most trustworthy group for transfusion safety (38,39). The number of repeat blood donors was much higher than the number of first-time blood donors (7,40 (42). Furthermore, it was lower than that of other countries such as Nigeria with 0.96% (24), Turkey with 0.20% (43) and India with 0.39% (22); however, a negative result was indicated for HIV in Punjab, Pakistan (23). The considerable differences in the prevalence of these infections among blood donors in different studies might be due to differences in the study population, sample sizes, study periods, the geographic regions, risk factors, methods used, the assay reagents and kits employed to determine the infectious agent (30). Moreover, we think that this lower prevalence of HIV in our study may be due to the traditional culture in Kohgiluyeh and Boyer-Ahmad Province so that, people believe sexual morality and avoiding of high-risk behaviors such as sexual relations with different partners before marriage.

Conclusion
A number of factors may have also attributed to declining prevalence: immunization against HBV; improved recruitment of low risk donors; the setup of confidential unit exclusion (CFU); the usage of a computerized data registry of blood donors for transfusion services; an increase in public knowledge of transfusion-transmissible infections, risk factors and transmission routes; improving public health programs; an increase in voluntary blood donation to 100%; an increasing number of regular/repeat donations; improvements in automation and using highly sensitive screening test kits. Despite all these endeavors, it is not feasible to eradicate the risks of TTIs.

Ethical considerations
Ethical issues (Including plagiarism, informed consent, misconduct, data fabrication and/or falsification, double publication and/or submission, redundancy, etc.) have been completely observed by the authors.